Serum levels of pigment epithelium-derived factor (PEDF) are inversely associated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

Tahara, Nobuhiro; Yamagishi, Sho‐ichi; Matsui, Takanori; Nishino, Yoshinori; Honda, Akihiro; Tahara, Atsuko; Igata, Sachiyo

doi:10.1016/j.ijcard.2015.02.010

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Among them, advanced glycation end products (AGEs), senescent macromolecule derivatives formed at an accelerated rate under hyperglycemic and oxidative stress conditions, play a crucial role in atherosclerotic cardiovascular disease of patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) [ 4 , 5 , 6 ]. Indeed, AGEs are localized in macrophage-derived foam cells within the atherosclerotic lesions and associated with endothelial dysfunction and arterial stiffness, being a prognostic marker of future cardiovascular events in T1D and T2D patients [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

A Dipeptidyl Peptidase-4 Inhibitor Inhibits Foam Cell Formation of Macrophages in Type 1 Diabetes via Suppression of CD36 and ACAT-1 Expression

Terasaki

Yashima

Mori

et al. 2020

IJMS

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Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to play a protective role against atherosclerosis in both animal models and patients with type 2 diabetes (T2D). However, since T2D is associated with dyslipidemia, hypertension and insulin resistance, part of which are ameliorated by DPP-4 inhibitors, it remains unclear whether DPP-4 inhibitors could have anti-atherosclerotic properties directly by attenuating the harmful effects of hyperglycemia. Therefore, we examined whether a DPP-4 inhibitor, teneligliptin, could suppress oxidized low-density lipoprotein (ox-LDL) uptake, foam cell formation, CD36 and acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) gene expression of macrophages isolated from streptozotocin-induced type 1 diabetes (T1D) mice and T1D patients as well as advanced glycation end product (AGE)-exposed mouse peritoneal macrophages and THP-1 cells. Foam cell formation, CD36 and ACAT-1 gene expression of macrophages derived from T1D mice or patients increased compared with those from non-diabetic controls, all of which were inhibited by 10 nmol/L teneligliptin. AGEs mimicked the effects of T1D; teneligliptin attenuated all the deleterious effects of AGEs in mouse macrophages and THP-1 cells. Our present findings suggest that teneligliptin may inhibit foam cell formation of macrophages in T1D via suppression of CD36 and ACAT-1 gene expression partly by attenuating the harmful effects of AGEs.

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Section: Introductionmentioning

confidence: 99%

A Dipeptidyl Peptidase-4 Inhibitor Inhibits Foam Cell Formation of Macrophages in Type 1 Diabetes via Suppression of CD36 and ACAT-1 Expression

Terasaki

Yashima

Mori

et al. 2020

IJMS

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“…It plays important roles in neuroprotection (21), angiogenesis (21), fibrogenesis (21), bone matrix mineralization (22), and inflammation (21). Although PEDF was first identified as being produced by retinal pigment epithelium cells, it is now known to be expressed in many tissues and cell types (23), including chondrocytes (24) and synovial cells (25), and it also naturally occurs in the serum (26) and SF (27). In addition to the many beneficial effects that PEDF may exert, it has also been implicated in the pathogenesis of several diseases, such as the chronic inflammatory diseases atherosclerosis (28) and type 2 diabetes (29), as well as certain brain tumors (30).…”

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confidence: 99%

Activation of Complement by Pigment Epithelium–Derived Factor in Rheumatoid Arthritis

Vogt

Talens

Kwasniewicz

et al. 2017

The Journal of Immunology

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The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.

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Relationship between serum pigment epithelium-derived factor and serum dipeptidyl peptidase-4

Kawada

2016

International Journal of Cardiology

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Serum levels of pigment epithelium-derived factor (PEDF) are inversely associated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

Cited by 4 publications

References 21 publications

A Dipeptidyl Peptidase-4 Inhibitor Inhibits Foam Cell Formation of Macrophages in Type 1 Diabetes via Suppression of CD36 and ACAT-1 Expression

A Dipeptidyl Peptidase-4 Inhibitor Inhibits Foam Cell Formation of Macrophages in Type 1 Diabetes via Suppression of CD36 and ACAT-1 Expression

Activation of Complement by Pigment Epithelium–Derived Factor in Rheumatoid Arthritis

Relationship between serum pigment epithelium-derived factor and serum dipeptidyl peptidase-4

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